Emmanuel Itti

This study aimed to assess the prognostic value of medullary total metabolic tumor volume (mTMTV) derived from fluorodeoxyglucose–positron emission tomography/computed tomography ([18F]FDG-PET/CT) compared with conventional PET-derived features and biological/chromosomal abnormalities in patients with newly diagnosed multiple myeloma (NDMM) treated with daratumumab for induction/consolidation and/or maintenance and enrolled in CASSIOPET, a companion study of CASSIOPEIA, with long-term follow-up. Automated bone/liver CT–based segmentation were applied to the baseline [18F]FDG-PET images, with mTMTV being defined using the median liver background as the cut-off, including focal lesions and diffuse bone marrow (BM) involvement. Both univariate/multivariate Cox and machine learning (ML)–based survival models were performed. A total of 195 patients were included, 81% of them PET-positive. Multivariate analysis demonstrated independent prognostic value of mTMTV for progression-free survival (PFS) (P< .001) and overall survival (OS) (P< .001), complementary to Revised International Staging System (R-ISS) (P = .008 and P< .001, respectively). The ML model confirmed these findings, achieving concordance index of 0.609 and 0.659 and identifying mTMTV as the most informative feature for PFS and OS. Adding R-ISS, BM maximum standardized uptake value (SUVmax) and anemia to mTMTV accounted for >60% of the ML model explanation for PFS and adding R-ISS, the number of focal lesions and BM SUVmax for >60% of the model for OS. Combining R-ISS and mTMTV enabled the creation of 2 new-risk subgroups. In conclusion, this prospective study demonstrated the prognostic relevance of [18F]FDG-PET/CT–based parameters in the initial workup of patients with NDMM in the era of anti-CD38–based therapy. mTMTV was found to have strong independent prognostic value, complementary to R-ISS and refining risk stratification. This trial was registered at www.clinicaltrials.gov as #NCT02541383.

The phase 2 ALYCANTE trial aimed to evaluate the investigator-assessed complete metabolic response at 3 months from the axicabtagene ciloleucel (axi-cel) infusion as a primary end point in patients with high-risk relapsed/refractory large B-cell lymphoma who are ineligible for autologous stem cell transplantation (ASCT). This study showed a significant improvement in complete metabolic response rate at 3 months based on historical controls. This study reports the health-related quality of life (HRQoL) results as a secondary end point. HRQoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) cancer-specific questionnaire, the Quality of Life Questionnaire high-grade non-Hodgkin lymphoma 29 (QLQ-NHL-HG29) , and the EuroQol Quality of Life Scale-5 dimensions-5 levels of severity (EQ-5D-5L) generic questionnaire at baseline and 1, 3, 6, and 12 months after axi-cel infusion. Among the 62 patients included, 60 (97%) completed a baseline and at least 1 postbaseline HRQoL assessment. At 1 month infusion, adjusted mean change in HRQoL scores from baseline showed a clinically significant deterioration (greater than the clinical threshold) in physical, role, social functioning, and fatigue. However, all HRQoL dimensions recovered by 3 months after infusion and remained stable or continued to improve by 12 months. In an exploratory analysis, adjusted mean change in HRQoL score from baseline in ALYCANTE was similar to or better than in ASCT-eligible patients who received axi-cel in the phase 3 ZUMA-7 trial. Finally, the global health status and fatigue scores of the ALYCANTE population improved to levels comparable to the general French population of similar age by 3 months after infusion. These findings indicate that axi-cel improves HRQoL regardless of transplant eligibility, supporting its use across a broad patient population. This trial was registered at www.clinicaltrials.gov as #NCT04531046.

The CASSIOPEIA trial demonstrated superior progression-free survival (PFS) with the addition of daratumumab to bortezomib, thalidomide, and dexamethasone (D-VTd) induction/consolidation, and with daratumumab maintenance vs observation in transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). The companion study, CASSIOPET, assessed the prognostic value of premaintenance (PM) positron emission tomography (PET)/computed tomography (CT) response, based on the standardized Deauville score on PFS and overall survival (OS), in addition to bone marrow (BM) minimal residual disease (MRD) detection by multiparameter flow cytometry (MFC) at 10–5 level. PM PET/CT was available for 225 patients: 112 patients treated with daratumumab after D-VTd (59) or bortezomib, thalidomide, and dexamethasone (VTd; 53), and 113 patients followed by observation after D-VTd (56) or VTd (57). At PM, 92% of the 175 baseline PET-positive patients achieved PET negativity, with a longer PFS in univariate analysis (P = .019) and a major trend of prolonged OS (P = .056). In univariate analysis, patients who achieved both PET and MFC negativity were found to have a better PFS (P < .0001) than those who had at least 1 positive result. In daratumumab-treated patients, PM PET negativity was associated with prolonged PFS and OS in univariate analysis (P = .0023 and P = .033, respectively), and double MFC and PET negativity was independently associated with PFS by multivariate analysis (P = .0006). This study confirms the prognostic relevance of a PM PET response in patients with NDMM treated with daratumumab in addition to MRD detection by MFC at the BM level. This trial was registered at ww.clinicaltrials.gov as #NCT02541383.

Patients with follicular lymphoma who experience disease progression within 24 months of diagnosis (POD24) have a lower survival. Positron emission tomography (PET) response and circulating tumor DNA (ctDNA) minimal residual disease (MRD) assessment at end of induction (EOI) may allow their early identification. A representative cohort of 141 patients from the RELEVANCE phase 3 trial with both available serum samples for ctDNA testing and PET images at randomization and at EOI (week 24) was investigated. Twelve percent were POD24. ctDNA was analyzed using a customized 130-kilobase capture panel, with phased variant (PV) enriched regions representing 39% of the panel. ctDNA was detected in 140 patients (99.3%) at baseline. To optimize specificity, only PVs, found in 124 patients (88%), were considered for ctDNA MRD assessment at EOI. Median progression-free survival (PFS) from EOI was not reached (NR) for the 112 patients with undetected ctDNA at EOI vs 17.7 months (95% confidence interval [CI], 1.4 to NR) for patients with positive ctDNA (MRD+) (P = .0038). Similarly, median PFS was NR for the 104 patients with undetected disease on PET at EOI vs 28.3 months (95% CI, 2.9 to NR; P = .0002) for patients with PET positivity. Both tests had a negative predictive value (NPV) of >90% for POD24. The positive predictive value was 58.3% for ctDNA MRD and 45% for PET but increased to 85.7% when both parameters were combined, without alteration of NPV. These data show that the combination of PET response and ctDNA MRD at EOI allows an early prediction of POD24, which may lead to a preemptive treatment decision. This trial was registered at www.clinicaltrials.gov as #NCT01650701.

The GAINED study was a randomized phase 3 trial comparing obinutuzumab (G) with rituximab (R) plus ACVBP (doxorubicin, cyclophosphamide, and prednisone, combined with either vindesine or bleomycin) or CHOP14 (cyclophosphamide, doxorubicin, vincristine, and prednisone, administered on a 14-day schedule) induction, followed by positron emission tomography (PET)–guided consolidation. This post hoc analysis aimed to detail the outcomes of patients with primary mediastinal B-cell lymphoma (PMBL), verified through expert pathological review and the use of gene expression profiling (GEP) and next-generation sequencing. Of 620 centrally reviewed patients, 138 (22.3%) confirmed PMBL cases were analyzed. Baseline characteristics included a median age of 33.5 years, 63.8% female, 55.1% stage III to IV, 90.6% elevated lactate dehydrogenase, 87.6% Eastern Cooperative Oncology Group performance status score of 0 to 1, 62.3% extranodal involvement, 52.6% age-adjusted International Prognostic Index (aaIPI) of 2% to 3%, and 53.6% bulk (>10 cm). Induction regimens were R/G-CHOP14 (56.9%) and R/G-ACVBP (43.1%). Postinduction treatments, based on interim PET results, included: standard consolidation chemotherapy (59.8%) if change in maximum standardized uptake value (ΔSUVmax) of >66% after cycle 2 and >70% after cycle 4 (PET2−/4−), intensive treatment and autologous transplantation (26.8%) if PET2+/4−, and salvage therapy (13.4%) if PET4+ (ΔSUVmax of ≤70%). Among patients with GEP data (n = 107), 38 (35.5%) were PDL1high/PDL2high. Key somatic mutations data (n = 87) included SOCS1 (70.1%), B2M (56.3%), STAT6 (49.4%), TNFAIP3 (47.1%), GNA13 (39.1%), CIITA (37.9%), CD58 (36.8%), and TP53 (29.9%). After a median follow-up of 39.5 months, 2-year progression-free survival (PFS) and overall survival (OS) rates were 86.2% and 93.2%, respectively. In a multivariate model including bulk, aaIPI, and ΔSUVmax PET2/PET4, only bulk and ΔSUVmax PET4 of ≤70% were associated with shorter PFS (hazard ratio, 4.39 [95% confidence interval (CI), 1.28-15.11] and 4.95 [95% CI, 1.71-14.3], respectively), whereas none were associated with OS. The ΔSUVmax-based interim PET4 response emerged as the strongest predictor of patient outcomes in this selected clinical trial population. This trial was registered at www.ClinicalTrials.gov as #NCT01659099.

Background: 18F-fluorodeoxyglucose positron emission tomography–CT (FDG-PET/CT) is useful for identifying infective endocarditis (IE) but also the detection of other concomitant septic foci. Previously, we found that FDG-PET/CT identified an osteoarthritic septic graft (OASG) in 19.1% of IE patients, frequently asymptomatic. These preliminary results encouraged us to extend our analyses to a larger population, including all patients initially explored for suspected IE, to assess the prevalence, characteristics, and OASG locations brought out by FDG-PET/CT and to identify predictive factors. Methods: From a single-center cohort of patients referred for a clinical and/or biological suspicion of IE, we included all patients who underwent FDG-PET/CT, mainly performed to confirm a prosthesis heart valve or a foreign cardiac device infection. We excluded those who did not meet the 2015 modified Duke Criteria and those for whom another infectious diagnosis was finally retained or for whom all bacterial samples were negative. Demographic, clinical, bacteriological, imaging, and therapeutic data were collected. FDG-PET/CT images were retrospectively analyzed by three blinded nuclear medicine specialists to identify OASGs. Results: We identified 72 distinct OASG locations by FDG-PET/CT in 48 of 174 patients (27.6%), mainly located in the spine (21 OASGs in 20 patients); 14 patients (8.0%) had several OASG locations. In total, 43.8% of OASG locations were asymptomatic. In multivariate analysis, the presence of OASGs was associated with musculoskeletal pain (p < 0.001) and tricuspid valve involvement (p = 0.002). Conclusions: FDG-PET/CT is useful for identifying OASGs in patients with suspected IE, especially those with tricuspid IE or musculoskeletal pain. The identification of OASGs could impact antibiotic therapy and would allow adapted orthopedic management to be proposed.

Background: Cardiac amyloidosis (CA) is frequently found in older patients with aortic stenosis (AS). However, the prevalence of AS among patients with CA is unknown. The objective was to study the prevalence and prognostic impact of AS among patients with CA. Methods and Results: We conducted a retrospective analysis of a prospective registry comprising 976 patients with native aortic valves who were confirmed with wild type transthyretin amyloid (ATTRwt), hereditary variant transthyretin amyloid (ATTRv), or immunoglobulin light‐chain (AL) CA. CA patients' echocardiograms were re‐analyzed focusing on the aortic valve. Multivariable Cox regression analysis was performed to assess the mortality risk associated with moderate or greater AS in ATTRwt CA. The crude prevalence of AS among patients with CA was 26% in ATTRwt, 8% in ATTRv, and 5% in AL. Compared with population‐based controls, all types of CA had higher age‐ and sex‐standardized rate ratios (SRRs) of having any degree of AS (AL: SRR, 2.62; 95% Confidence Interval (CI) [1.09–3.64]; ATTRv: SRR, 3.41; 95%CI [1.64–4.60]; ATTRwt: SRR, 10.8; 95%CI [5.25–14.53]). Compared with hospital controls, only ATTRwt had a higher SRR of having any degree of AS (AL: SRR, 0.97, 95%CI [0.56–1.14]; ATTRv: SRR, 1.27; 95%CI [0.85–1.44]; ATTRwt: SRR, 4.01; 95%CI [2.71–4.54]). Among patients with ATTRwt, moderate or greater AS was not associated with increased all‐cause death after multivariable adjustment (hazard ratio, 0.71; 95%CI [0.42–1.19]; P =0.19). Conclusions: Among patients with CA, ATTRwt but not ATTRv or AL is associated with a higher prevalence of patients with AS compared with hospital controls without CA, even after adjusting for age and sex. In our population, having moderate or greater AS was not associated with a worse outcome in patients with ATTRwt.

Introduction and aim: Simultaneous positron emission tomography/magnetic resonance imaging (PET-MRI) combines the high sensitivity of PET with the high specificity of MRI and is a tool for the assessment of gastroenteropancreatic neuroendocrine neoplasms (G-NENs). However, it remains poorly evaluated with no clear recommendations in current guidelines. Thus, we evaluated the prognostic impact of PET-MRI in G-NEN patients. Methods: From June 2017 to December 2021, 71 G-NEN patients underwent whole-body PET-MRI for staging and/or follow-up purposes. A whole-body emission scan with ¹⁸F-6-fluoro-L-dihydroxyphenylalanine (¹⁸FDOPA, n = 30), ¹⁸F-fluoro-2-deoxy-D-glucose (¹⁸FDG, n = 21), or ⁶⁸Ga-(DOTA(0)-Phe(1)-Tyr(3))-octreotide (⁶⁸Ga-DOTATOC, n = 20) with the simultaneous acquisition of a T1-Dixon sequence and diffusion-weighed imaging (DWI), followed by a dedicated step of MRI sequences with a Gadolinium contrast was performed. The patients underwent PET-MRI every 6–12 months during the follow-up period until death. Over this period, 50 patients with two or more PET-MRI were evaluated. Results: The mean age was 61 [extremes, 31–92] years. At the baseline, PET-MRI provided new information in 12 cases (17%) as compared to conventional imaging: there were more metastases in eight, an undescribed location (myocardia) in two, and an unknown primary location in two cases. G grading at the baseline influenced overall survival. During the follow-up (7–381 months, mean 194), clinical and therapy managements were influenced by PET-MRI in three (6%) patients due to new metastases findings when neither overall, nor disease-free survivals in these two subgroups (n = 12 vs. n = 59), were different. Conclusion: Our study suggests that using PET/MRI with the appropriate radiotracer improves the diagnostic performance with no benefit on survival. Further studies are warranted to evaluate the cost-effectiveness of this procedure.